Introduction
The prevalence of frailty syndrome increases with age in the community-dwelling older adults, and has been reported to range from 4 to 59% [7]. Risk factors of frailty syndrome include increasing age, iron-deficiency anemia, vision loss, history of stroke, and female gender [9, 10]. Iron-deficiency anemia in older adults is often neglected due to its mild manifestations. It can play a role in the development of frailty syndrome [11, 13]. Therefore, the present study aimed to investigate the relationship between iron-deficiency anemia and frailty syndrome in Iranian older adults.

Methods
This is a cross-sectional study based on the Bushehr Elderly Health (BEH) Cohort Study. The first phase of this cohort study was conducted in two stages from February 2013 to September 2014 (lasted 2.5 years), and the second phase was conducted from September 2015 to February 2018. A total of 3,000 people (men and women) aged ≥60 were selected using a multistage cluster random sampling method and based on the inclusion criteria from a population of approximately 10,000 people (based on information from the Bushehr Health Center).
The inclusion criteria were: age ≥60 years, residing in Bushehr Port for at least one year before the start of the study and not planning to leave the city for the next 2 years, having sufficient physical and mental ability to participate in the program, and signing a written informed consent form. Of the 3297 participants who met the inclusion criteria, 3000 participants agreed to participate (participation rate: 91.0%). Of the 3,000 people who participated in the first phase, 2,426 remained in the second phase of the study (participation rate: 80%) and 574 dropped out due to death, immigration, or unwillingness to continue participation in the study. They were measured once a year, and a form was given to participants to report as soon as possible after the occurrence of each of the specified outcomes. The measurements were done by questionnaires (A demographic form, the international physical activity questionnaire, and the mini nutritional assessment scale), physical examinations, and laboratory tests, which were done by trained nurses through face-to-face interviews with the elderly. STATA software, version 17 was used for data analysis.

Results
Among 3000 participants, 1545(51.50%) were women and 1455(48.5%) were men. In terms of marital status, 2248 were married (74.93%) and the rest were single, widow/widower or divorced. Their mean hemoglobin level was 14.49±1.73 g/dL, which is within the normal range according to the criteria defined by the World Health Organization. The participants were in two groups of with and without frailty syndrome. The mean age of older adults with frailty syndrome was 73.83±7.76 years. The mean hemoglobin level in the patient group was 14.18±1.76 g/dL, while in non-frail individuals it was 14.56±1.72 g/dL, and this difference was statistically significant (P=0.002). The prevalence of iron-deficiency anemia was 13.92% in the patient group and 8.11% in the healthy group, with a significant difference (P=0.002).
The univariate regression results showed that the frailty syndrome was significantly associated with anemia, depression, age, systolic blood pressure, hemoglobin level, educational level, feeling of tiredness, income level, walking speed, psychical activity, and hand grip strength (P<0.05). According to univariate regression analysis results, it was found that walking speed was directly related to the incidence of frailty. For each one unit increase in walking time over a 4-m distance, the likelihood of developing frailty increases by 4.08 units. The hand grip strength and hemoglobin level were inversely related to the risk of developing frailty. For each one unit increase in grip strength and hemoglobin level, the likelihood of developing frailty decreases by 7% and 13%, respectively. Height also had a significant and inverse relationship; For each one unit increase in height, the risk of frailty decreases by 4 times. 
According to multiple logistic regression analysis results, iron-deficiency anemia was directly related to the incidence of frailty; for each one unit increase in anemia, the risk of frailty increases by 3.23 units. Moreover, for each one unit increase in age and walking speed, the likelihood of developing frailty syndrome increases by 1.15 and 19.10 units. Moreover, for each one unit increase in height and hand grip strength, the likelihood of developing frailty syndrome decreases by 1.16 and 1.24 units (Table 1).



Conclusion
The iron-deficiency anemia and low hemoglobin level are significantly associated with frailty syndrome in Iranian older adults. There is also a significant relationship between frailty syndrome and variables related to physical performance, such as hand grip strength and walking speed. Anemic older people are more inactive and had a sedentary lifestyle, which affects their physical performance and leads to decreased muscle mass and strength. According to the results of the present study, attention to the level of primary care, diagnosis and treatment of iron-deficiency anemia, early screening, and health interventions can be used to prevent, delay, or even reverse frailty in Iranian older adults.

Ethical Considerations

Compliance with ethical guidelines
This study was approved by the Ethics Committee of Shahid Sadoughi University of Medical Sciences, Yazd, Iran (Code: IR.SSU.SPH.REC.1400.002).

Funding
This article was extracted from a master's thesis of Zeinab Bahrani, approved by Shahid Sadoughi University of Medical Sciences, Yazd, Iran. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 

Authors' contributions
All authors contributed equally to the conception and design of the study, data collection and analysis, interpretation of the results, and drafting of the manuscript. Each author approved the final version of the manuscript for submission.

Conflicts of interest
The authors declare no conflict of interest.

Acknowledgments
The authors would like to thank all the staff of the BEH Center, Sand the seniors who participated in this study for their cooperation and assistance.
 

 

1. Zakizadeh R, Bahreini M, Farhadi A, Bagherzadeh R. [Predictive role of loneliness in mental health of elderly people in Bushehr (Persian)]. Iranian Journal of Psychiatric Nursing. 2020; 7(6):71-8. [Link]
2. Cruz RR, Beltrame V, Dallacosta FM. Aging and vulnerability: An analysis of 1,062 elderly persons. Revista Brasileira de Geriatria e Gerontologia. 2019; 22(03):e180212. [DOI:10.1590/1981-22562019022.180212]
3. Barbosa da Silva A, Queiroz de Souza I, da Silva IK, Borges Lopes Tavares da Silva M, Oliveira Dos Santos AC. Factors associated with frailty syndrome in older adults. The journal of nutrition, health & aging. 2020; 24(2):218-22. [DOI:10.1007/s12603-020-1310-y] [PMID]
4. Mulla E, Montgomery U. Frailty: An overview. InnovAiT. 2020; 13(2):71-9. [DOI:10.1177/1755738019890891]
5. Akten IM, Akin S. Frailty in older adults: Assessment and management. Recent Studies in Health Sciences. 2019:659. [Link]
6. Bernabeu-Wittel M, González-Molina Á, Fernández-Ojeda R, Díez-Manglano J, Salgado F, Soto-Martín M, et al. Impact of sarcopenia and frailty in a multicenter cohort of polypathological patients. Journal of Clinical Medicine. 2019; 8(4):535. [DOI:10.3390/jcm8040535] [PMID] 
7. Rohrmann S. Epidemiology of frailty in older people. Advances in Experimental Medicine and Biology. 2020; 1216:21-7. [DOI:10.1007/978-3-030-33330-0_3] [PMID]
8. Shaheen M, Puri S, Tandon N. An overview of frailty in elderly. Journal of the Indian Academy of Geriatrics. 2016; 12(2):58-65. [DOI:10.35262/jiag.v12i2.58-65]
9. Ofori-Asenso R, Chin KL, Mazidi M, Zomer E, Ilomaki J, Zullo AR, et al. Global incidence of frailty and prefrailty among community-dwelling older adults: A systematic review and meta-analysis. JAMA Network Open. 2019; 2(8):e198398. [DOI:10.1001/jamanetworkopen.2019.8398] [PMID] 
10. Gu J, Chen H, Gu X, Sun X, Pan Z, Zhu S, et al. Frailty and associated risk factors in elderly people with health examination in rural areas of China. Iranian Journal of Public Health. 2019; 48(9):1663-70. [PMID]
11. Lamba R, Agarwal A, Rana R, Agarwal V. Prevalence of anemia and its correlates among elderly population of an urban slum in meerut. Journal of the Indian Academy of Geriatrics. 2019; 15(3):109-14. [DOI:10.35262/jiag.v15i3.109-114]
12. Juárez-Cedillo T, Basurto-Acevedo L, Vega-García S, Manuel-Apolinar L, Cruz-Tesoro E, Rodríguez-Pérez JM, et al. Prevalence of anemia and its impact on the state of frailty in elderly people living in the community: SADEM Study. Annals of Hematology. 2014; 93(12):2057-62. [DOI:10.1007/s00277-014-2155-4] [PMID]
13. Girelli D, Marchi G, Camaschella C. Anemia in the elderly. HemaSphere. 2018; 2(3):e40. [DOI:10.1097/HS9.0000000000000040] [PMID] 
14. Andrès E, Vogel T, Zulfiqar A. Anemia in elderly patients: State of art, with a focus on nutritional anemia. In: Means Jr RT, editor. Anemia in the young and old: Diagnosis and management. Cham: Springer; 2019. [DOI:10.1007/978-3-319-96487-4_11] 
15. Marzban M, Nabipour I, Farhadi A, Ostovar A, Larijani B, Darabi AH, et al. Association between anemia, physical performance and cognitive function in Iranian elderly people: Evidence from Bushehr Elderly Health (BEH) program. BMC Geriatrics. 2021; 21(1):329. [DOI:10.1186/s12877-021-02285-9] [PMID] 
16. Ostovar A, Nabipour I, Larijani B, Heshmat R, Darabi H, Vahdat K, et al. Bushehr elderly health (BEH) Programme, phase I (cardiovascular system). BMJ open. 2015; 5(12):e009597. [DOI:10.1136/bmjopen-2015-009597] [PMID] 
17. Shafiee G, Ostovar A, Heshmat R, Darabi H, Sharifi F, Raeisi A, et al. Bushehr Elderly Health (BEH) programme: Study protocol and design of musculoskeletal system and cognitive function (stage II). BMJ Open. 2017; 7(8):e013606. [DOI:10.1136/bmjopen-2016-013606] [PMID] 
18. Hagströmer M, Oja P, Sjöström M. The International Physical Activity Questionnaire (IPAQ): A study of concurrent and construct validity. Public Health Nutrition. 2006; 9(6):755-62. [DOI:10.1079/PHN2005898] [PMID]
19. Bieniek J, Wilczyński K, Szewieczek J. Fried frailty phenotype assessment components as applied to geriatric inpatients. Clinical Interventions in Aging. 2016; 11:453-9. [DOI:10.2147/CIA.S101369] [PMID] 
20. WHO. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Geneva: World Health Organization; 2011. [Link]
21. Hoffbrand V, Provan D. ABC of clinical haematology. Macrocytic anaemias. BMJ. 1997; 314(7078):430-3. [DOI:10.1136/bmj.314.7078.430] [PMID] 
22. Roberts HC, Denison HJ, Martin HJ, Patel HP, Syddall H, Cooper C, et al. A review of the measurement of grip strength in clinical and epidemiological studies: Towards a standardised approach. Age and Ageing. 2011; 40(4):423-9. [DOI:10.1093/ageing/afr051] [PMID]
23. Kelishadi R, Rabiei K, Khosravi A, Famouri F, Sadeghi M, Rouhafza H, et al. [Assessment of physical activity of adolescents in Isfahan (Persian)]. Journal of Shahrekord University of Medical Sciences. 2001; 3(2):55-66. [Link]
24. Aadahl M, Jørgensen T. Validation of a new self-report instrument for measuring physical activity. Medicine and Science in Sports and Exercise. 2003; 35(7):1196-202. [DOI:10.1249/01.MSS.0000074446.02192.14] [PMID]
25. Alley DE, Shardell MD, Peters KW, McLean RR, Dam TT, Kenny AM, et al. Grip strength cutpoints for the identification of clinically relevant weakness. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences. 2014; 69(5):559-66. [DOI:10.1093/gerona/glu011] [PMID] 
26. Xue QL, Bandeen-Roche K, Varadhan R, Zhou J, Fried LP. Initial manifestations of frailty criteria and the development of frailty phenotype in the Women’s Health and Aging Study II. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2008; 63(9):984-90. [DOI:10.1093/gerona/63.9.984] [PMID]
27. de Assis EPS, de Macêdo BG, da Silva TAM, Rezende PdPD, Vieira ÉLM, Junior ALT, et al. Association between frailty syndrome and anemia in community-dwelling elderly. Advances in Aging Research. 2019; 8(5):75-87. [DOI:10.4236/aar.2019.85006]
28. Ma L, Chhetri JK, Chan P. Frailty in China: From research to practice. The Journal of Nutrition, Health & Aging. 2021; 25(4):479-83. [DOI:10.1007/s12603-021-1593-7] [PMID]
29. Katsumi A, Abe A, Tamura S, Matsushita T. Anemia in older adults as a geriatric syndrome: A review. Geriatrics & Gerontology international. 2021; 21(7):549-54. [DOI:10.1111/ggi.14183] [PMID]
30. Lee CT, Chen MZ, Yip CYC, Yap ES, Lee SY, Merchant RA. Prevalence of anemia and its association with frailty, physical function and cognition in community-dwelling older adults: Findings from the HOPE study. The Journal of Nutrition, Health and Aging. 2021; 25(5):679-87. [DOI:10.1007/s12603-021-1625-3] [PMID]
31. Steinmeyer Z, Delpierre C, Soriano G, Steinmeyer A, Ysebaert L, Balardy L, et al. Hemoglobin concentration; a pathway to frailty. BMC Geriatrics. 2020; 20(1):202. [DOI:10.1186/s12877-020-01597-6] [PMID] 
32. Ruan Y, Guo Y, Kowal P, Lu Y, Liu C, Sun S, et al. Association between anemia and frailty in 13,175 community-dwelling adults aged 50 years and older in China. BMC Geriatrics. 2019; 19(1):327.[DOI:10.1186/s12877-019-1342-5] [PMID] 
33. Pires Corona L, Drumond Andrade FC, de Oliveira Duarte YA, Lebrao ML. The relationship between anemia, hemoglobin concentration and frailty in Brazilian older adults. The Journal of Nutrition. 2015; 19(9):935-40. [DOI:10.1007/s12603-015-0502-3] [PMID]
34. Gi YM, Jung B, Kim KW, Cho JH, Ha IH. Low handgrip strength is closely associated with anemia among adults: A cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES). PLoS One. 2020; 15(3):e0218058.[DOI:10.1371/journal.pone.0218058] [PMID] 
35. Walston J, Arking DE, Fallin D, Li T, Beamer B, Xue Q, et al. IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women. Experimental Gerontology. 2005; 40(4):344-52. [DOI:10.1016/j.exger.2005.01.012] [PMID] 
36. Kim EY, Son YJ. Association between anemia and cognitive impairment among elderly patients with heart failure. International Journal of Environmental Research and Public Health. 2019; 16(16):2933. [DOI:10.3390/ijerph16162933] [PMID] 
37. Ni T, Liu Y, Huang M, Ma M, Li L, Li C, et al. Association between anemia status and the risk of different types of heart failure: A RCSCD-TCM study in China. Angiology. 2024; 75(2):190-6. [DOI:10.1177/00033197231161908] [PMID]
38. Zhang H, Wei X, Chen X, Sun X. Mortality from all-cause and cause-specific in the elderly: Joint implications of anemia and frailty. Archives of Gerontology and Geriatrics. 2023; 115:105213. [DOI:10.1016/j.archger.2023.105213] [PMID]
39. Maraldi C, Ble A, Zuliani G, Guralnik JM, Mussi C, Fellin R, et al. Association between anemia and physical disability in older patients: Role of comorbidity. Aging Clinical and Experimental Research. 2006; 18(6):485-92. [DOI:10.1007/BF03324848] [PMID]